Our previous study showed that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), the most biotoxic polybrominated diphenyl ether (PBDE) in the marine environment, induced apoptosis in rainbow trout gonadal RTG-2 cells. This effect occurred via ROS- and Ca2+-mediated apoptotic pathways, but the exact mechanism remains unknown. Therefore, in the present study, the possible mechanism was examined from the perspective of ROS-induced oxidative stress. The results showed that BDE-47 exposure significantly elevated the malondialdehyde (MDA) contents and the intracellular GSH/GSSG ratio, and the GSH-related enzymes were greatly altered, indicating alteration of the redox status and occurrence of oxidative stress. The mRNA levels of nuclear factor E2-related factor 2 (Nrf2) and its downstream genes were simultaneously greatly elevated. The p38 mitogen-activated protein kinase (MAPK) signaling pathway was also found to be induced by BDE-47 exposure. The addition of SB203580, a p38 MAPK inhibitor resulted in decreased apoptosis. In addition, supplementation with Ca2+ inhibitors BAPTA-AM positively affected p38 MAPK activation. Taken together, BDE-47 exposure resulted in the occurrence of oxidative stress and initiated the Nrf2-mediated antioxidant response. Subsequently, the altered redox status induced p38 MAPK activation, which played a pivotal role in the cellular apoptosis of RTG-2 cells.Azobenzene disperse dyes are the fastest-growing class of dyestuffs, yet little is known about dye occurrences, sources, and transformations; azo dyes are also underrepresented in chemical standard catalogs, molecular databases, and mass spectral libraries. Many azo dyes are known to have sensitization, mutagenic, and carcinogenic properties. To fill these knowledge gaps, azo dyes were purified from dyestuffs by Soxhlet extraction and flash chromatography and characterized using ultra-high-performance liquid chromatography (UHPLC) coupled to a high resolution Orbitrap Fusion Lumos mass spectrometer operated in positive electrospray ionization mode, as well as by 1H and 13C NMR. Data were analyzed to identify likely chemical formulas and structures using a weight-of-evidence approach with multiple open-source, in silico computational mass spectrometry tools. Nineteen total azobenzene dyes were detected in dyestuffs via a non-targeted analysis approach; the azobenzene dyes Disperse Blue 791, Disperse Blue 1831, Disperse Orange 44, Disperse Orange 73, Disperse Red 50, Disperse Red 73, and Disperse Red 354 were purified from raw dyestuffs. Samples of children's polyester clothing were then analyzed likewise. In clothing, 21 azobenzene disperse dyes were detected, 12 of which were confirmed and quantified via reference standards. Individual dyes in apparel were quantified at concentrations up to 9230 μg dye/g shirt, with geometric means ranging 7.91-300 μg dye/g shirt. Total dye load in apparel was quantified at up to 11,430 μg dye/g shirt. This research supported the development of reference standards and library mass spectra for azobenzene disperse dyes previously absent from standard and spectral libraries. By analyzing the scope and quantities of azo dyes in children's polyester apparel, this study will facilitate a more robust understanding of sources of these potentially allergenic and mutagenic compounds.The historical air pollution with halogenated flame retardants (HFRs) in Germany was assessed by investigating tree leaf and shoot samples which have been archived in the German environmental specimen bank. Samples covered the period from 1985 to 2016. 43 HFRs comprising polybrominated diphenyl ethers as well as emerging brominated and chlorinated compounds such as Dechlorane Plus, DBDPE, or DPTE, were analysed in 115 samples from ten sub sites originating from six areas characterised by different land uses, including urban as well as a background site. HFRs were observed in each sample showing the widespread distribution of HFRs in Germany in tree leaves and shoots as bioindicators of past and present atmospheric pollution. Analytes observed at elevated concentrations were BDE 209, DBDPE and DPTE. Observed HFR-levels differed between analytes as well as sampling locations, particularly prior to the year 2000. They were typically highest at conurbation areas. Concentrations at the background site often belonged to the lowest ones observed, however, lowest values were not exclusively found there. The quantification frequencies appeared to decrease from the past to most recent samples. With few exceptions, atmospheric pollution of both, legacy and emerging HFRs, decreased significantly.Our current understanding of the molecular mechanisms underlying activation of store-operated Ca2+ entry (SOCE) relies in large part on studies that modulate the expression of STIM1 and Orai1. Shen et al. present the first detailed study to address the dynamics and stoichiometry of endogenous STIM1 and Orai1. They argue for an active SOCE cluster centered around a single Orai1 channel per punctum linked to 12 STIM1 dimers, which could have significant implications on SOCE-dependent Ca2+ signaling.The aim of the current study was to investigate the risk factors for post-traumatic epilepsy (PTE) in a large cohort of patients after severe non-penetrating civilian traumatic brain injury (TBI).
This was a longitudinal study. All patients with a severe non-penetrating TBI, who were admitted at the neuro-intensive care unit of Shahid Rajaee Trauma Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran, from 2015 until 2019, were studied. Severe TBI was defined as a Glasgow Coma Scale-Motor score below six. Post-traumatic epilepsy was defined as any seizures that occurred after being discharged from the hospital.
In total, 803 patients with severe non-penetrating TBI were studied; 82 patients (10.2%) reported any late post-traumatic seizures (PTSs). https://www.selleckchem.com/ A higher Glasgow outcome scale (extended) at discharge was significantly inversely associated with PTE [Odds Ratio (OR)= 0.76, 95% Confidence Interval (CI) 0.65-0.87; p=0.0001]. Depressed skull fracture (OR= 1.88, 95% CI 0.92-3.80; p=0.